Anti-cytokine and anti-hyperalgesic effects of aliskiren in experimental models of inflammation

Abstract

The renin‐angiotensin system is involved in pathogenesis and progression of
inflammatory responses. In present study, we investigated the anti-cytokine and
anti-hyperalgesic potential of aliskiren in LPS (lipopolysaccharide) and CFA
(complete Freund’s adjuvant) induced inflammation in rodents. After aliskiren
treatment, plasma cytokines (TNF-, IL-6) and plasma renin activity (PRA) were
estimated in LPS treated mice. In CFA induced inflammatory pain model, rats
were treated with aliskiren and thermal hyperalgesia was evaluated and TNF-
and IL-6 were estimated in paw. In LPS treated ICR mice, elevated TNF- and
IL-6 levels and PRA were attenuated by aliskiren. In LPS treated double
transgenic mice (dTG), harboring human renin and human angiotensinogen and
C57BL/6J mice, elevated TNF- level was inhibited by aliskiren. Moreover after
LPS treatment, TNF- level was high (2.16 fold) in dTG mice than C57BL/6J.
These data indicates that renin overexpression system in dTG mice is
responsible for higher TNF- level suggests role of renin in inflammation.
Moreover, Aliskiren showed anti-hyperalgesic activity in CFA induced
inflammatory hyperalgesia in rats, which might be due to inhibition TNF- and IL-
6 levels, suggests the role of local renin in inflammation. Our results indicate the
role of renin in experimental inflammation which is inhibited by aliskiren.